An experimental model of human endometrial carcinoma has been developed, in which human tumors are grown and passaged in nude mice with maintenance of their biochemical and morphological characteristics. The progesterone receptor has been characterized and partially purified from tumors grown in nude mice, and monoclonal antibodies have been prepared. These experimental tools, and the ability to sensitively modulate the progesterone receptor in this experimental system place us in an ideal position to study the physicochemical characteristics of purified progesterone receptor proteins, which in turn, will serve as the basis for comparison with the altered characteristics of these proteins during the regulation of progesterone receptor in vivo. Therefore, the specific aims of this proposal are 1) to study the structure of human endometrial carcinoma PR 2) to investigate the regulation of PR structure, 3) to determine the relationship between PR structure and biological response and 4) to analyze the mechanism of down regulation of PR by progestins. These studies will significantly advance our understanding of the biology of progestin action in endometrial carcinoma which is the longterm objective of this proposal.